Work

Lewis Acid-Catalyzed Vinyl Acetal Rearrangement of 4,5-Dihydro-1,3-dioxepines: Stereoselective Synthesis of cis- and trans-2,3-Disubstituted Tetrahydrofurans

Year: 2020

Type: article

Abstract: Lewis acid-catalyzed rearrangements of 4,5-dihydro-1,3-dioxepines have been investigated. Rearrangement of vinyl acetals under a variety of conditions resulted in cis - and trans- 2,3-disubstituted tetrahydrofuran derivatives in a highly stereoselective manner. Rearrangements at lower temperatures typically provided the cis -2,3-disubstituted tetrahydrofuran carbaldehydes. At higher temperatures, the corresponding trans -2,3-disubstituted tetrahydrofuran carbaldehydes are formed. The requisite substrates for the vinyl acetal rearrangement were synthesized via ring-closing olefin metathesis of bis(allyoxy)methyl derivatives using Grubbs second-generation catalyst followed by olefin isomerization using a catalytic amount of RuCl 2 (PPh 3 ) 3 . We examined the substrate scope using substituted aromatic and aliphatic derivatives. Additionally, the rearrangement was utilized in the synthesis of a stereochemically-defined bis-tetrahydrofuran (bis-THF) derivative, which is one of the key structural elements of darunavir, an FDA-approved drug for the treatment of HIV/AIDS.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.0c00390

Authors: Arun K. Ghosh, Miranda R. Belcher

Institution: Purdue University West Lafayette

Language: English

Topic: Organic Chemistry Synthesis Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of Allergy and Infectious Diseases

Awards: G4403659332, Cancer Center Support Grant, Design & Synthesis of Nonpeptide Protease Inhibitors, Design & Synthesis of Nonpeptide Protease Inhibitors